• 中国科技论文统计源期刊
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Volume 45 Issue 10
Nov.  2020
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Effect of bifidobacterium triple viable preparation on the postoperative recovery of patients with upper gastrointestinal perforation

  • Corresponding author: ZAN Jian-bao, zanjb@sina.com
  • Received Date: 2019-09-02
    Accepted Date: 2020-01-02
  • ObjectiveTo investigate the safety and effectiveness of bifidobacterium triple viable preparation in the postoperative recovery of patients with upper gastrointestinal perforation.MethodsSixty patients with upper gastrointestinal perforation were divided into the observation group and control group by random number table method(30 cases in each group).The control group was treated with early enteral nutrition based on the basic treatment regimen, and the observation group was treated with bifidobacterium triple viable preparation preparation based on the control group.The total white blood cell count(WBC), neutrophil ratio, C-reactive protein(CRP), procalcitonin(PCT), interleukin-6(IL-6), CD3+T cells, CD4+ T cells, CD8+T cells, CD4+/CD8+ and other indicators were detected in two groups, and the hospital stay and incidence rate of complications were recorded.ResultsThe differences of the levels of WBC, neutrophil ratio, CRP, PCT, IL-6 and T lymphocyte subsets between two groups before and after 1 and 4 days of surgery were not statistically significant(P>0.05).After 4 days of surgery, the neutrophil ratio and IL-6 level in observation group were lower than those in control group(P < 0.05).After 7 days of surgery, the WBC and neutrophil ratio in two groups basically returned to normal, and the difference of which was not statistically significant(P>0.05), and the levels of CRP, PCT and IL-6 in observation group were lower than those in control group(P < 0.05 to P < 0.01).After 4 and 7 days of operation, the proportions of CD3+ T cells and CD4+ T cells, and CD4+/CD8+ in observation group were higher than those in control group(P < 0.05 to P < 0.01), the proportion of CD8+ T cells in observation group was significantly lower than that in control group(P < 0.01).The length of hospital stay and incidence rate of complications in observation group were lower than those in control group(P < 0.01 and P < 0.05).ConclusionsThe bifidobacterium triple viable preparation in the treatment of upper gastrointestinal perforation can strengthen the immunity of patients, reduce systemic inflammatory reaction, enhance intestinal barrier, promote rapid recovery of intestinal function and reduce the incidence of postoperative complications, which is worthy of promotion in clinic.
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  • [1] 沈通一, 秦环龙.微生态制剂在结直肠外科围手术期的应用[J/CD].中华结直肠疾病电子杂志, 2017, 6(2): 98.
    [2] 赵晓志.X线透视下置入鼻空肠重力管操作技巧探讨[J].河北医科大学学报, 2015, 36(1):95.
    [3] 任建安, 崔乃强, 傅强.急性弥漫性腹膜炎对全身免疫功能的影响[J].中国实用外科杂志, 2009, 29(6):520.
    [4] 张鑫, 郭军.益生菌与肠道黏膜免疫研究进展[J].畜牧与饲料科学, 2017, 38(11):58.
    [5] LACHAR J, BAJAJ JS.Changes in the microbiome in cirrhosis and relationship to complications:Hepatic encephalopathy, spontaneous bacterial peritonitis, and sepsis[J].Semin Liver Dis, 2016, 36(4):327. doi: 10.1055/s-0036-1593881
    [6] BIESALSKI HK.Nutrition meets the microbiome:Micronutrients and the microbiota[J].Ann N Y Acad Sci, 2016, 1372(1):53. doi: 10.1111/nyas.13145
    [7] GUO S, GILLINGHAM T, GUO Y, et al.Secretions of bifidobacterium infantis and Lactobacillus acidophilus protect intestinal epithelial barrier function[J].J Pediatr Gastroenterol Nutr, 2017, 64(3):404. doi: 10.1097/MPG.0000000000001310
    [8] BHATTARAI Y, SCHMIDT BA, LINDEN DR, et al.Human-derived gut microbiota modulates colonic secretion in mice by regulating 5-HT3 receptor expression via acetate production[J].Am J Physiol Gastrointest Liver Physiol, 2017, 313(1):G80. doi: 10.1152/ajpgi.00448.2016
    [9] 李守付.胃十二指肠溃疡穿孔修补术后早期肠内营养的效果及安全性[J].山东医药, 2015, 55(45):52.
    [10] 张舒龙, 朱勇.腹腔镜胃十二指肠溃疡穿孔修补术临床疗效分析[J].蚌埠医学院学报, 2014, 39(1):83.
    [11] KINROSS JM, MARKAR S, KARTHIKESALINGAM A, et al.A meta-analysis of probiotic and synbiotic use in elective surgery:Does nutrition modulation of the gut microbiome improve clinical outcome?[J].J Parenter Enteral Nutr, 2013, 37(2):243. doi: 10.1177/0148607112452306
    [12] YANG Y, XIA Y, CHEN H, et al.The effect of perioperative probiotics treatment for colorectal cancer:Short-term outcomes of a randomized controlled trial[J].Oncotarget, 2016, 7(7):8432. doi: 10.18632/oncotarget.7045
    [13] 李锦春, 钱传云, 蔡乙明, 等.微生态制剂联合肠内营养对急性重症胰腺炎患者全身炎症反应、细菌移位以及免疫功能的影响[J].中国现代医学杂志, 2018, 28(6):85.
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Effect of bifidobacterium triple viable preparation on the postoperative recovery of patients with upper gastrointestinal perforation

    Corresponding author: ZAN Jian-bao, zanjb@sina.com
  • Department of General Surgery, Anqing Hospital Affiliated to Anhui Medical University, Anqing Anhui 246003, China

Abstract: ObjectiveTo investigate the safety and effectiveness of bifidobacterium triple viable preparation in the postoperative recovery of patients with upper gastrointestinal perforation.MethodsSixty patients with upper gastrointestinal perforation were divided into the observation group and control group by random number table method(30 cases in each group).The control group was treated with early enteral nutrition based on the basic treatment regimen, and the observation group was treated with bifidobacterium triple viable preparation preparation based on the control group.The total white blood cell count(WBC), neutrophil ratio, C-reactive protein(CRP), procalcitonin(PCT), interleukin-6(IL-6), CD3+T cells, CD4+ T cells, CD8+T cells, CD4+/CD8+ and other indicators were detected in two groups, and the hospital stay and incidence rate of complications were recorded.ResultsThe differences of the levels of WBC, neutrophil ratio, CRP, PCT, IL-6 and T lymphocyte subsets between two groups before and after 1 and 4 days of surgery were not statistically significant(P>0.05).After 4 days of surgery, the neutrophil ratio and IL-6 level in observation group were lower than those in control group(P < 0.05).After 7 days of surgery, the WBC and neutrophil ratio in two groups basically returned to normal, and the difference of which was not statistically significant(P>0.05), and the levels of CRP, PCT and IL-6 in observation group were lower than those in control group(P < 0.05 to P < 0.01).After 4 and 7 days of operation, the proportions of CD3+ T cells and CD4+ T cells, and CD4+/CD8+ in observation group were higher than those in control group(P < 0.05 to P < 0.01), the proportion of CD8+ T cells in observation group was significantly lower than that in control group(P < 0.01).The length of hospital stay and incidence rate of complications in observation group were lower than those in control group(P < 0.01 and P < 0.05).ConclusionsThe bifidobacterium triple viable preparation in the treatment of upper gastrointestinal perforation can strengthen the immunity of patients, reduce systemic inflammatory reaction, enhance intestinal barrier, promote rapid recovery of intestinal function and reduce the incidence of postoperative complications, which is worthy of promotion in clinic.

  • 上消化道穿孔是临床上最常见的急腹症之一,多数由上消化道溃疡引起,具有发病急、病情重、死亡率高等特点。而急性弥漫性腹膜炎是其最主要的并发症,急性上消化道穿孔常需外科干预或手术治疗,目前临床上多采用急诊腹腔镜手术方式,术后予以抗菌、抑酸、胃肠减压、营养支持等对症治疗。随着加速康复外科理念不断地深入临床,如何最大程度地促进病人术后康复,减少术后并发症及住院时间成为关注的重点。近年来,将肠道微生态制剂应用于腹部外科手术围手术期,用来维护肠道微生态、恢复肠道正常的生理和代谢功能,正越来越受到重视[1]

1.   资料与方法
  • 选择2018年5月至2019年6月在我院住院治疗的60例上消化道穿孔病人作为研究对象,根据随机数字表法分为观察组和对照组,各30例。观察组男23例,女7例,年龄17~75岁;11例胃穿孔,19例十二指肠穿孔。对照组男25例,女5例,年龄16~75岁;9例胃穿孔,21例十二指肠穿孔。2组病人的性别、年龄及穿孔类型差异均无统计学意义(P>0.05)(见表 1)。纳入标准:(1)诊断急性上消化道穿孔的病人;(2)病人伴有较重的急性弥漫性腹膜炎,曼海姆腹膜炎指数(MPI)>15~ < 26;(3)急诊行腹腔镜穿孔修补术的病人;(4)病人年龄14~75岁;(5)签订知情同意书者。排除标准:(1)合并严重多器官功能障碍综合征(MODS)或多脏器衰竭(MOF)病人,急性生理与慢性健康评分(APACHEⅡ评分)≥20分或MPI≥26;(2)全身免疫功能极差(中性粒细胞 < 2×109/L),或获得性免疫缺陷综合症病人;(3)腹膜炎范围小,症状轻,病程短,MPI < 16;(4)开腹手术病人;(5)肠道功能严重受损,长时间不能进行肠内营养的病人,如术后发生肠瘘、肠梗阻病人;(6)术后确诊为肿瘤引起的穿孔的病人。初入选病人共67例,其中5例因满足排除标准(5),2例因满足排除标准(6)未完成实验。60例完成试验的病人均康复出院。

    分组 n 年龄/岁 胃穿孔 十二指肠穿孔
    观察组 30 23 7 50.07±16.74 11 19
    对照组 30 25 5 50.93±15.79 9 21
    χ2 0.42 0.20Δ 0.30
    P > 0.05 > 0.05 > 0.05
      Δ示t
  • 基础治疗方案:使用带空肠营养管的胃管行胃肠减压、禁经口进食、急诊行腹腔镜穿孔修补术、广谱抗生素抗感染、抑酸、营养支持、调节电解质及酸碱平衡等,术后要求病人适当进行床上活动,并在帮助下逐步过渡到下床活动。

  • 在基础治疗方案之上加入术后早期肠内营养,具体如下:术前在X线辅助下,经鼻置入含胃管的空肠营养管[2](浙江衢州市迅康医疗器械有限公司生产,专利号ZL032294352)。术后第2天开始经空肠营养管利用输液泵输注肠内营养混悬液(百普力,无锡纽迪希亚制药有限公司,国药准字H20010285),采用斜坡体位,在适宜温度下先慢后快地输注,首日500 mL,逐日增加,3~4 d后增至1 000 mL/d,维持至术后一周,之后根据病人病情恢复情况逐渐增加经口进食,并调整肠内营养用量。

  • 在对照组的基础上,加入肠道微生态制剂,具体如下:肠内营养同对照组,通过空肠营养管注入溶于少量温水(≤40 ℃)的双歧杆菌三联活菌胶囊(培菲康,上海信谊药厂有限公司,国药准字S10950032),2次/天,4粒/次。

  • 2组病人均于入院后术前和术后第1、4、7天分别抽血测白细胞总数(WBC)及中性粒细胞比例、C反应蛋白(CRP)、降钙素原(PCT)、白细胞介素6(IL-6)、CD3+T细胞、CD4+ T细胞、CD8+T细胞、CD4+/CD8+等指标,并记录住院时间及并发症(包括肺部感染、切口感染、腹胀、腹泻、腹腔感染性积液、术后早期炎性肠梗阻等)发生情况。使用日本希森美康公司XE2100型全自动血细胞分析仪测定白细胞及中性粒细胞,使用罗氏全自动生化分析仪测定CRP及PCT水平,使用西门子Ⅰ1000型化学发光分析仪测定IL-6水平,通过流式细胞分析仪测定外周血T淋巴细胞亚群。

  • 采用t检验、χ2检验、方差分析和q检验。

2.   结果
  • 术前及术后第1、4天,2组病人WBC、中性粒细胞比例、CRP、PCT、IL-6水平差异均无统计学意义(P>0.05)。术后第4天,观察组病人的中性粒细胞比例和IL-6水平低于对照组(P < 0.05)。术后第7天,2组病人的WBC及中性粒细胞比例均基本恢复正常,差异无统计学意义(P>0.05),观察组病人的CRP、PCT及IL-6水平低于对照组(P < 0.05~P < 0.01)(见表 2)。

    分组 术前 术后第1天 术后第4天 术后第7天 F P MS组内
    WBC/(×109/L)
       观察组 12.90±4.06 10.76±3.37 7.23±1.77 6.09±1.36**##▲ 36.16 < 0.01 8.219
       对照组 12.29±4.07 10.50±3.42 7.79±2.17 6.70±1.75**## 25.89 < 0.01 8.998
          t 0.58 0.04 1.10 1.51
          P > 0.05 > 0.05 > 0.05 > 0.05
    中性粒细胞比例/%
       观察组 89.07±5.45 84.50±7.45 65.53±7.64 57.87±6.68**##▲ 142.2 < 0.01 47.020
       对照组 88.53±5.22 83.80±7.18 69.80±8.05 60.83±7.86**##▲ 93.94 < 0.01 51.355
          t 0.39 0.37 2.11 1.57
          P > 0.05 > 0.05 < 0.05 > 0.05
    CRP/(mg/L)
       观察组 36.67±74.91 112.24±70.36 57.86±35.19 10.74±6.04##▲ 18.85 < 0.01 2 559.279
       对照组 35.09±76.30 110.81±72.36 64.25±40.54 17.10±11.84##▲ 15.63 < 0.01 3 210.571
          t 0.08 0.08 0.65 2.62
          P > 0.05 > 0.05 > 0.05 < 0.05
    PCT/(ng/mL)
       观察组 6.66±9.49 15.32±17.76 2.58±2.06 0.31±0.17**##▲ 12.81 < 0.01 102.421
       对照组 6.36±9.55 14.11±19.10 3.43±3.93 0.52±0.37*#▲ 8.70 < 0.01 117.949
          t 0.12 0.25 0.93 2.82
          P > 0.05 > 0.05 > 0.05 < 0.01
    IL-6/(pg/mL)
       观察组 27.72±20.23 41.93±21.99 25.96±12.15 11.16±3.62**##▲ 18.03 < 0.01 263.352
       对照组 28.43±20.80 41.35±22.72 33.81±17.09 18.16±8.56##▲ 8.68 < 0.01 328.540
          t 0.13 0.10 2.05 4.13
          P > 0.05 > 0.05 < 0.05 < 0.01
      q检验:与术前比较*P < 0.05,**P < 0.01;与术后第1天比较#P < 0.05,## P < 0.01;与术后第4天比较▲P < 0.05
  • 术前及术后第1、4天,2组病人的外周血T淋巴细胞亚群水平差异无统计学意义(P>0.05)。术后第4、7天,观察组CD3+、CD4+ T淋巴细胞比例、CD4+/CD8+较对照组高(P < 0.05~P < 0.01),CD8+T淋巴细胞比例明显低于对照组(P < 0.01)(见表 3)。

    分组 术前 术后第1天 术后第4天 术后第7天 F P MS组内
    CD3 +T淋巴细胞/%
       观察组 48.42±12.62 42.71±11.10 56.49±8.07 62.37±5.10**##▲ 24.19 < 0.01 93.411
       对照组 49.14±12.58 43.08±10.97 50.40±8.60 55.74±7.45## 7.95 < 0.01 102.028
          t 0.22 0.13 2.83 4.02
          P > 0.05 > 0.05 < 0.05 < 0.01
    CD4+T淋巴细胞/%
       观察组 26.91±5.35 23.54±3.32 28.08±2.39 31.60±2.89**##▲ 24.70 < 0.01 13.442
       对照组 26.49±4.60 23.76±2.89 26.55±2.33 28.53±1.81##▲ 11.88 < 0.01 9.702
          t 0.33 0.27 2.51 4.93
          P > 0.05 > 0.05 < 0.05 < 0.01
    CD8+T淋巴细胞/%
       观察组 40.65±4.98 47.06±4.14 30.55±2.70 24.16±2.35**##▲ 228.72 < 0.01 13.697
       对照组 41.28±4.66 46.18±3.37 34.44±3.20 28.48±3.09**##▲ 136.57 < 0.01 13.205
          t 0.51 0.90 5.01 6.10
          P > 0.05 > 0.05 < 0.01 < 0.01
    CD4+/CD8+
       观察组 0.68±0.19 0.51±0.10 0.93±0.12 1.32±0.17**##▲ 166.63 < 0.01 0.022
       对照组 0.66±0.17 0.52±0.09 0.78±0.11 1.02±0.15**##▲ 73.78 < 0.01 0.018
          t 0.43 0.41 5.05 7.25
          P > 0.05 > 0.05 < 0.01 < 0.01
      q检验:与术前比较*P < 0.05,**P 0.01;与术后第1天比较# P 0.05,##P < 0.01;与术后第4天比较▲P < 0.05
  • 观察组病人的住院时间和术后并发症发生率低于对照组(P < 0.01和P < 0.05)(见表 4)。

    分组 住院时间/d 术后并发症
    观察组 10.80±2.01 5(16.7)
    对照组 12.63±1.75 12(40.0)
    χ2 3.76* 4.02
    P < 0.01 < 0.05
      *示t
3.   讨论
  • 随着世界各国肠道微生物宏基因组学的不断发展,人们对其了解愈发深入。肠道菌群具有人体“第二基因组”的称号,对于人体健康有着无法替代的作用。它参与营养吸收、能量代谢、组织器官发育、免疫防御和内分泌调节等多种生命活动,与人类健康密切相关。

    上消化道穿孔病人存在严重的肠道菌群紊乱。首先,胃或十二指肠穿孔直接破坏消化道的机械屏障,导致细菌移位。其次,手术刺激、麻醉和术后禁食会导致胃肠蠕动减弱,肠道功能恢复迟缓,肠道微生态平衡受到破坏。此外,围手术期使用多种广谱抗生素,非选择性地灭杀抑制肠道细菌,进一步加重肠道菌群紊乱,造成肠道菌群移位、肠源性内毒素血症,引起全身炎症反应综合征,进一步恶化可演变为MODS和感染性休克,甚至死亡。

    在上消化道穿孔引起的腹腔感染过程中,存在淋巴细胞凋亡的现象。脓毒症早期,细菌及其毒素引起免疫细胞的活化和增殖,大量的炎症介质产生,导致促炎和抗炎反应失衡。通过多种机制,各种免疫细胞相继有不同形式的凋亡。随着炎症反应的持续,T、B淋巴细胞凋亡加速,免疫功能下降易感性增加。如果不及时干预,可能形成恶性循环[3]

    本研究使用的肠道微生态制剂是双歧杆菌三联活菌胶囊(由长型双歧杆菌、噬乳酸杆菌和粪肠球菌组成),其主要作用有:(1)抗菌、增强免疫作用,益生菌的部分代谢产物有对抗致病菌生长繁殖的作用,乳酸菌不仅能抑制病原体的复制繁殖,还可以增强脾中自然杀伤细胞的活性[4],本研究中,术后第4天及术后第7天,观察组CD3+、CD4+ T淋巴细胞比例及CD4+/CD8+高于对照组,CD8+T淋巴细胞比例明显低于对照组,表明双歧杆菌三联活菌胶囊能提高病人的细胞免疫功能。(2)生物屏障作用,益生菌是肠黏膜屏障的重要组成部分,具有定殖性、繁殖性及排他性,在肠黏膜上皮细胞通过磷壁酸结合,占领肠黏膜表层,形成化学屏障及生物学屏障,以防止致病菌的定植入侵。当肠道微生态因各种原因被破坏,致病菌大量增殖及移位,引起肠源性菌血症,致病菌及其毒素大量生成并侵袭至肠外器官,即破坏了肠道屏障功能[5]。CRP、PCT、IL-6均为临床常用的反映机体炎症反应的检测指标,本研究中,术后第4天,观察组病人的中性粒细胞比例、IL-6水平低于对照组,2组病人CRP及PCT差异无统计学意义,可能是因为肠道微生态制剂作用时间尚短或样本量不足,导致差异并不明显,术后第7天,观察组病人血清中的CRP、PCT、IL-6水平低于对照组,表明双歧杆菌三联活菌胶囊能有效降低病人的炎症反应,加速病情康复。(3)营养作用,益生菌参与机体多种维生素的合成代谢过程,供人体健康所需。乳酸菌可以通过降低肠道pH值,促进铁、维生素D和钙、磷的吸收利用,还参与B族维生素的合成和吸收[6]。(4)促进肠道功能恢复作用,乳酸杆菌和双歧杆菌可以促进Caco-2细胞中黏蛋白的表达,抑制NF-κB的表达来控制肠道渗透压保持在正常范围,改善肠道的功能[7]。益生菌还可以影响神经肽的分泌,例如5-羟色胺能促进肠道平滑肌的收缩,影响肠蠕动状态。有研究[8]表明,通过向大鼠肠道内置入人体的肠道细菌,5-羟色胺的分泌量显著增多。本研究中,观察组病人的住院时间和术后并发症发生率均低于对照组,表明使用双歧杆菌三联活菌胶囊的病人术后恢复更好、更快。

    在快速康复外科理念的指导下,2组病人均采用术后早期肠内营养治疗,并不要求病人所需的能量完全由肠内营养提供,而是要尽快恢复肠道功能,并为肠道益生菌群的生长和繁殖提供营养环境。早期肠内营养并不会增加术后并发症的发生率,反而有利于伤口愈合。肠内营养有助于促进肠蠕动,维持正常的肠道结构和生理功能,保证肠黏膜的完整性,促进肠道微生态的恢复,减少细菌移位和肠源性细菌感染的发生率[9]。本研究中的大多数病人能够很好地耐受肠内营养。一些病人在应用早期出现腹胀或腹部绞痛。停止输注6~12 h,并在恢复后继续输注。该实验采用的手术方式为腹腔镜胃十二指肠溃疡穿孔修补术,相较于开腹手术,有着安全性高、创伤小、恢复快等优点[10]

    肠道微生态制剂已在腹部外科应用多年。目前,它常用于结直肠癌、胃癌、肝脏等手术围手术期及重症胰腺炎的治疗。一项纳入962例病人的Meta分析[11]指出,在普外科择期手术围手术期应用微生态制剂,可显著降低术后脓毒症的总体发生率。有研究[12]报道益生菌可改善结肠切除术后胃肠功能,可缩短首次排便时间,减少败血症等并发症的发生。李锦春等[13]用微生态制剂治疗急性重症胰腺炎病人,结果表明微生态制剂组可显著降低病人的全身炎症反应,减少致病菌移位,促进病人病情康复。

    综上所述,应用双歧杆菌三联活菌胶囊治疗急性上消化道穿孔,能增强病人的免疫力,减少全身炎症反应,增强肠道屏障,促进病人快速恢复,值得临床应用。

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